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Function
Polycomb group (PcG) proteins are determinants of gene silencing and epigenetic memory in higher eukaryotes. The PcG system consists of multimeric repressive protein complexes containing chromatin modifying activities which regulate transcription by modulating chromatin structures. The PcG proteins regulate pathways in cell differentiation, tissue regeneration and cancer cell growth[1]. For the B-cell-specific Molony leukemia virus Insertion site 1 (BMI1) see BMI1.
- Pcgf5 and Polycomb SUZ12 are required in the differentiation of embryonic stem cells toward neural cells[2], [3].
- Pcgf6 has a critical role in safeguarding lineage decisions and in preventing aberrant expression of germ cell-related genes[4].
- Polycomb EED is a component of Polycomb repressive complex 2 (PRC2) and is an epigenetic exchange factor coordinating the activities of PRC1 and PRC2[5].
- Polycomb SCMH1 is a component of Polycomb repressive complex 1 (PRC1) and is involved in sex chromosomes[6].
- Polycomb Sfmbt downregulates genes of the synaptonemal complex during meiosis[7].
- Polycomb Asx in Drosophila is required for maintenance of stable repression of homeotic loci[8].
- Polycomb repressive complex 2 or PRC2 methylates histone H3. PRC2 is composed of polycomb EED, SUZ12 and enhancer EZH as a minimal core [9].
See also: Polycomb complex protein.
Disease
Misregulation of PcG protein levels often lead to either a block or unscheduled activation of developmental pathways. the consequences of this misregulation have been linked to the establishment of cancer stem cells which can produce tumors. Cancer stem cells are believed to persist within tumors and to elicit relapse and metastasis[10]
Structural highlights
- ↑ Hauri S, Comoglio F, Seimiya M, Gerstung M, Glatter T, Hansen K, Aebersold R, Paro R, Gstaiger M, Beisel C. A High-Density Map for Navigating the Human Polycomb Complexome. Cell Rep. 2016 Oct 4;17(2):583-595. doi: 10.1016/j.celrep.2016.08.096. PMID:27705803 doi:https://dx.doi.org/10.1016/j.celrep.2016.08.096
- ↑ Yao M, Zhou X, Zhou J, Gong S, Hu G, Li J, Huang K, Lai P, Shi G, Hutchins AP, Sun H, Wang H, Yao H. PCGF5 is required for neural differentiation of embryonic stem cells. Nat Commun. 2018 May 15;9(1):1463. doi: 10.1038/s41467-018-03781-0. PMID:29765032 doi:https://dx.doi.org/10.1038/s41467-018-03781-0
- ↑ Pasini D, Bracken AP, Hansen JB, Capillo M, Helin K. The polycomb group protein Suz12 is required for embryonic stem cell differentiation. Mol Cell Biol. 2007 May;27(10):3769-79. PMID:17339329 doi:10.1128/MCB.01432-06
- ↑ Liu M, Zhu Y, Xing F, Liu S, Xia Y, Jiang Q, Qin J. The polycomb group protein PCGF6 mediates germline gene silencing by recruiting histone-modifying proteins to target gene promoters. J Biol Chem. 2020 Jul 10;295(28):9712-9724. doi: 10.1074/jbc.RA119.012121. Epub , 2020 Jun 1. PMID:32482889 doi:https://dx.doi.org/10.1074/jbc.RA119.012121
- ↑ Cao Q, Wang X, Zhao M, Yang R, Malik R, Qiao Y, Poliakov A, Yocum AK, Li Y, Chen W, Cao X, Jiang X, Dahiya A, Harris C, Feng FY, Kalantry S, Qin ZS, Dhanasekaran SM, Chinnaiyan AM. The central role of EED in the orchestration of polycomb group complexes. Nat Commun. 2014;5:3127. PMID:24457600 doi:10.1038/ncomms4127
- ↑ Takada Y, Isono K, Shinga J, Turner JM, Kitamura H, Ohara O, Watanabe G, Singh PB, Kamijo T, Jenuwein T, Burgoyne PS, Koseki H. Mammalian Polycomb Scmh1 mediates exclusion of Polycomb complexes from the XY body in the pachytene spermatocytes. Development. 2007 Feb;134(3):579-90. PMID:17215307 doi:10.1242/dev.02747
- ↑ Feijão T, Marques B, Silva RD, Carvalho C, Sobral D, Matos R, Tan T, Pereira A, Morais-de-Sá E, Maiato H, DeLuca SZ, Martinho RG. Polycomb group (PcG) proteins prevent the assembly of abnormal synaptonemal complex structures during meiosis. Proc Natl Acad Sci U S A. 2022 Oct 18;119(42):e2204701119. PMID:36215502 doi:10.1073/pnas.2204701119
- ↑ Sinclair DA, Milne TA, Hodgson JW, Shellard J, Salinas CA, Kyba M, Randazzo F, Brock HW. The Additional sex combs gene of Drosophila encodes a chromatin protein that binds to shared and unique Polycomb group sites on polytene chromosomes. Development. 1998 Apr;125(7):1207-16. PMID:9477319
- ↑ Chammas P, Mocavini I, Di Croce L. Engaging chromatin: PRC2 structure meets function. Br J Cancer. 2020 Feb;122(3):315-328. doi: 10.1038/s41416-019-0615-2. Epub 2019 , Nov 11. PMID:31708574 doi:https://dx.doi.org/10.1038/s41416-019-0615-2
- ↑ Poynter ST, Kadoch C. Polycomb and trithorax opposition in development and disease. Wiley Interdiscip Rev Dev Biol. 2016 Nov;5(6):659-688. doi: 10.1002/wdev.244., Epub 2016 Sep 1. PMID:27581385 doi:https://dx.doi.org/10.1002/wdev.244
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